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Preventive actions are advised since the use of anti-tumor necrosis factor (TNF) agents is known to increase the risk of tuberculosis (TB). No data related to the effectiveness and safety of the preventive chemoprophylaxis (ChP) for TB in inflammatory bowel disease (IBD) patients are available. The goal was to evaluate the requirements, effectiveness, and safety profile of ChP in IBD patient candidates for anti-TNF therapy.All IBD patients diagnosed with latent TB while evaluated for anti-TNF therapy from the IBD database of 9 Spanish centers were included. Epidemiological and clinical data, risk factors for hepatotoxicity, ChP regimens, and side effects were registered.Sixty-three out of 497 IBD evaluated patients (12.5%) had latent TB. Sixty-eight percent were on immunomodulators and 42% on systemic corticosteroids when a TB skin test (TST) was performed. The detection of a positive TST was done in 86% after a single exposure, but 14% needed a booster. All but 1 were treated with isoniazid alone for 6 or 9 months, and only 1 case required ChP discontinuation because of hepatotoxicity. No risk factors for hepatotoxicity were found. No cases of active TB were noticed in the 67 patients further treated with anti-TNF therapy.More than 10% of Spanish IBD patients who are candidates for anti-TNF therapy have latent TB. TST retest is required to identify at least 14% of such patients; therefore, it should be considered if the initial TST is negative. ChP is safe in IBD patients even in those taking concomitant, potentially hepatotoxic drugs.